Amorphous silica nanocarriers: a novel chemotherapeutic approach for triple negative breast cancer

Abstract

Triple negative breast cancer (TNBC) is a heterogeneous group of tumors with difficult clinical management, due to the lack of the mo- lecular targets to the conventional chemotherapeutics. Nanotech- nology represents a strategy to overcome this problem employing nanocarriers that guide drugs to the tumoral site. Previously, we have reported the synthesis, characterization and viability effects on TNBC cell lines of two novel amorphous silica nanoparticles (NPs), Si@NH2 and Si@FA, the last modified with folic acid. The aim of this work is to continue with these preclinical studies, elucidating their mechanism of action and performing biocompatibility assays. Trans- mission electron microscopy (TEM) was used to examine the mor- phology of NPs. Cell cycle was analysed with propidium iodide (PI) staining in MDA-MB-231 cells after 24 and 48 h of treatment (NPs at 500 μg/mL). Apoptotic cells were quantified by Annexin V-FITC + PI staining. Histological evaluation of the organs of an in vivo assay that has been previously reported was performed. The haemolytic effect on red blood cells was evaluated by determination of free hae- moglobin on plasma obtained from the treatment of blood exposed to 10-500 μg/ml of each NP. The results show that TEM micrographs revealed monodisperse spherical shape for NPs, with biocompatible size. Both NPs induced cell cycle arrest in G0/G1 phase at 24 h (p < 0.001) and cell death at 48 h of treatment. The percentage of cells in early apoptosis was higher in Si@FA treated cells with respect to control (p < 0.01). The histological analysis of the internal organs did not demonstrate differences in mice treated with NPs in respect with control mice. Neither NPs induced haemolysis since free haemoglo- bin was quantified as less than 10 mg/dl. Altogether, these results suggest the potential use of Si@FA as nanocarrier for TNBC treat- ment. Further studies are in course to evaluate the incorporation of conventional chemotherapeutics.